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Using the chiral ligand (-)- sparteine as additive, the asymmetric allylation of ortho-methoxydiphenylmethane (I) is carried out with e.e.

A novel methodology for the asymmetric synthesis of trans-3,4-diaryl-substituted tetrahydroquinolines via sparteine-assisted stereoselective lithiation of o-substituted N-pivaloylanilines (I), kinetic resolution of epoxides in substitution and a stereospecific Mitsunobu cyclization is developed.

The preparation and synthetic application of novel copper(II)/(+)-sparteine surrogates are described.

The (+)-sparteine-mediated lithiation–substitution of o-benzyl-N-pivaloylaniline with various ketones was investigated. The obtained highly enantioenriched tertiary alcohols were used for the synthesis of alkenyl-substituted products 12 and 13 as well as 3,3,4-trisubstituted tetrahydroquinoline derivatives 22–24. The reaction with α,β-unsaturated ketones afforded highly enantioenriched 1,4-addition products 28–33 and provided a protocol for the asymmetric synthesis of highly substituted tetralin derivative 34.

The easy to prepare dimeric bis(?-iodo)bis[(-)-sparteine]- dicopper ([CuI{(-)-spa}] 2 complex) is shown to be versatile catalyst for O-arylation and O-alkylation with various aryl halides with phenols and aliphatic alcohols respectively, including less reactive aryl chlorides, such as chlorobenzene under mild conditions.

The dicopper(I)-complex is a versatile catalyst for the cross-coupling of a broad spectrum of aryl halides, where the bromides are generally the most suitable ones.

In this perspective we discuss the recent developments of stereoselective synthesis of substituted pyridines, piperidines, and piperazines from cheap and commercially readily available starting materials. Pyridine N-oxides and pyrazine N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to give a diverse set of heterocycles in high yields. Optically active substituted piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal-oximes from the reaction between pyridine N-oxides and Grignard reagents is presented, which results in a useful intermediate for the synthesis of a diverse set of compounds.

In most cases a reversal in the enantioselectivity of the title reactions is observed changing the catalysts metal atom from copper to nickel.

The cationic complex [Pd(η 3 -C 3 H 5 )(sparteine)]PF 6 ( 6 ) was found to be a suitable catalyst precursor for the asymmetric alkylation of allylic acetates with Na[CH(COOMe) 2 ] as the nucleophile. This constitutes one of the first and still rare examples of a phosphine-free system for this type of Pd-catalyzed reaction. Using 5 mol % of 6 , alkylation products were obtained in up to 90% isolated yield and 85 % enandomeric excess. The alkylation reaction was shown to occur with overall retention of configuration, indicating an analogous mechanism to the one previously proposed for phosphine-containing catalysts. The reactivity of allylic acetates is strongly dependent upon the nature of the substituents, open-chain aliphatic substrates being unreactive.

The preferentially formed (−)-sparteine complex from 1-lithio-2-butenyl N,N -diisopropylcarbamate has ( S )-configuration at the metal bearing carbon atom, in contrary to our previous assumption. Transmetallation with titanium tetraisopropoxide and the carboxylation proceed with inversion. The addition of aldehydes occurs in a anti -S E′ -process. The enantioselective synthesis of homoaldol adducts and some corresponding γ-lactones is reported.

Prostereogenic mono- and dicarbamates of 1,3-propanediol and 1,4-butanediol are deprotonated by the sec-butyllithium(−)-sparteine system with high enantiotopic differentiation. The electrophilic substitution of the intermediate chiral carbanions furnishes the title compounds with >;95% ee.

This review presents some considerations on the influence of inter- and extramolecular factors of bisquinolizidine alkaloids on their stereochemistry, chemical and physicochemical properties/also : proton-acceptor/ and configurational-conformational equilibria

The title compound (S)-3/(−)-2, easily available through deprotonation of the racemic O-(2-alkenyl) carbamate under kinetic resolution, undergoes with carbon dioxide or methyl chloroformate predominantly α-substitution with stereoinversion. The absolute configuration of the formed methyl carboxylate is established by chemical correlation, thus correcting our former suggestion3a.

Three different mechanisms have been identified for the CuCl 2 -mediated oxidative coupling of naphthols to binaphthyls in the presence of chiral amines (sparteine or α-methylbenzylamine); fair to excellent enantioselection has been observed (up to 100 % ee). The choice of the dominant mechanism appears to be critically dependent on the structure of the partners to be coupled. Thus, for the self-coupling of 2-naphthol (1) the enantioselection is mainly controlled of via a second-order asymmetric transformation of the product 4 (up to 100 % ee). The same mechanism is responsible for the formation of enantiomerically enriched biphenanthrol 9 (76% ee). By contrast, enantiodifferentiation in the formation of 5 and 7 results from the diastereoselective crystallization of the corresponding Cu(II)-amine-binaphtyl complex, wheras an enantioselective coupling operates in the preparation of 6. A catalytic cycle has been designed, employing 10 mol% of CuCl 2 (with AgCl to regenerate Cu II ) and sparteine(20 mol%); when applied to the asymmetric cross-coupling 1+3→6, the product (-)6 was obtained in 41%yield

Oxabicyclo[3.2.1]octenes have been found to undergo enantioselective ring opening in the presence of a catalytic quantity of the chiral amine sparteine.

Asymmetric [2,3]-Wittig rearrangements of allyl propargyl ethers in hexane were performed in the presence of s-butyllithium and (-)--isosparteine which is a -symmetric chiral ligand for the alkyllithium reagent. The reactions of (Z)-or (E)-allyl 3-trimethylsilylpropargyl ethers at -78 showed good diastereoselectivities (74-100%) and moderate enantioselectivities (29-71%). The absolute configurations of the rearrangement products were determined by the corresponding Mosher's esters. It was found that (-)- -isosparteine induced (R) configuration at the hydroxy carbon and syn stereochemistry more favorably. The possible transition state is discussed.

The intramolecular Schmidt reaction was applied to the norbornane skeleton to examine an approach to sparteine. In so doing, the stereospecificity of intramolecular Schmidt reactions of e-azido ketones was demonstrated. The intramolecular Schmidt reaction was found to fail in a ketone containing a lactam moiety.

The deprotonation of β-stereogenic alkyl carbamates 8 with sec-butyllithium/TMEDA proceeds kinetically controlled with differentiation between the diastereotopic protons at the α-methylene group. The lithium intermediates 9A and 9B are trapped by electrophiles to give carboxylic acid esters 10A/B and stannanes 11A/B, 13A/B. The diastereomeric ratio of A to B is independent of the electrophile. The highest efficiency is achieved with β-aryl-β-alkyl-substituted starting compounds 8d–f. The trends in the experimentally observed diastereoselectivities are reflected by the results of semiempirical PM3 calculations on the transition states of the deprotonation reaction. — As a result of double stereodifferentiation, application of the chiral base sec-butyllithium/(-)-sparteine gives rise to efficient kinetic resolution of racemic alkyl carbamates.

Highly enantioselective syntheses of (S)-2-aryl-Boc-pyrrolidines (Boc = tert-butoxycarbonyl) can be achieved by treatment of the corresponding (arylmethyl)(3-chloropropyl)-Boc-amines with s-BuLi/(−)-sparteine. The reactions are solvent dependent with the phenyl, p-chlorophenyl, p-fluorophenyl, p-methylphenyl, m-methoxyphenyl, 1-naphthyl, and 2-naphthyl derivatives 1−7 providing 11−17 in yields of 46−75% with enantiomeric excesses of 84−96% in toluene. The 2-thienyl and 3-furyl analogs 8 and 9 afford the (S)-2-heteroaryl-Boc-pyrrolidines 18 and 19 in 51 and 21% yields with 93−96% enantiomeric excesses. The p-methoxyphenyl derivative 10 gives 20 as a racemic product in 42% yield under the same conditions. Reactions of n-BuLi/(−)-sparteine with 1 and 8 give results comparable to those with s-BuLi/(−)-sparteine. Illustrative syntheses of (S)-2-phenyl-(S)-5-methyl-Boc-pyrrolidine (22) and 1,2-(bis-(S)-2-phenylpyrrolindyl)ethane (23) are reported. The mechanism of the reaction is shown to be an asymmetric depro...

A TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxyl)-modified graphite felt electrode afforded enantioselective, electrocatalytic lactonized products of (S)-(−)-3,4,5,6-tetrahydro-4-methyl-2-pyranone, (S)-(−)-4,5-dihydro-4-methyl-2(3H)-furanone and (S)-(−)-4,5-dihydro-5-methyl-2(3H)-furanone from 3-methylpentane-1,5-diol, (S)-(−)-2-methylbutane-1,4-diol and racemic pentane-1,4-diol, respectively, in enantiomeric excess more than 95%, in the presence of (−)-sparteine in acetonitrile. The current efficiency and isolated yield of former two lactones were more than 90%.

Stoichiometric or catalytic amounts of (−) sparteine serve as promoter for enantioselective carbolithiation of β-alkylated, non functionalized styrene. © 1997 Published by Elsevier Science Ltd.

“Chiral carbanions”—that is, enentiomerically enriched lithium–carbanion pairs in which the carbanionic center carries the chiral information—were regarded until recently as “exotic species.” In the past ten years it has become clear that they can, in fact, play a meaningful role in enantioselective synthesis, since substitution for lithium occurs here stereospecifically, usually with retention of configuration. They are also more readily and commonly accessible than was originally assumed. The trick lies in the use of lithium cations with chiral ligands, whether in the form of alkyllithium species used as bases in kinetically controlled, enantiotopically discriminating deprotonation, or in thermodynamically controlled equilibration in configurationally labile epimeric ion pairs. The lupine alkaloid (−)-sparteine has shown itself admirably suited as a chiral bidentate ligand, and its efficiency and breadth of application are so far unsurpassed. This contribution constitutes an overview of the preparation of chiral reagents, convering primarily “umpoled” synthons such as homoenolates. 1-oxyalkanides with a broad pattern of substitution, and α-aminobenzyl anions.

The [2,3] sigmatropic rearrangement of α-propargyloxyacetic acids was achieved by the use of BuLi-(-)-sparteine complex in toluene. BuLi-chiral ligand complexes are stronger bases than lithium amides, so they are expected to be good mediators of this reaction.

The first examples of an enantioselective [1,2] silicon rearrangement are reported. This novel synthetic method lead to the formation of chiral α-substituted benzylamines with an α-silyl group. In the procedure, N-Silyl-protectedN-Boc benzylamines are subjected to enantioselective deprotonation using the chiral complex (−) sparteine. s-BuLi to generate chiral benzyllithium intermediates that undergo a [1,2] silicon shift.

Three diastereoisomers of 1-deoxycastanospermine were synthesized in enantiomerically pure form. The key step in the synthesis involved reaction of lithiated N-Boc-pyrrolidine in the presence of sparteine with a chiral building block derived from tartaric acid.

Deracemization of diarylmethane derivatives was investigated by lateral lithiation–protonation mediated by (−)-sparteine. Treatment of racemic 4-phenyltetrahydroisoquinoline 1 with s-butyllithium–(−)-sparteine followed by protonation of the resulting anion afforded (R)-phenyltetrahydroisoquinoline 1 in up to 88% e.e. Following the same procedure, racemic 2-(1-phenylethyl)pyridine 2 was subjected to the lithiation–protonation sequence. The stereochemical outcome of the sequence proved to be highly dependent on the proton sources giving either (S)- or (R)-2-(1-phenylethyl)pyridine 2 with EtOH or t-BuOH respectively in up to 50% e.e.

Treatment of ( E )-6-phenyl-5-hexenyl carbamates with s -BuLi/(−)-sparteine is shown to afford the trans -1,2-disubstituted cyclopentane derivatives in high % ee, along with the bicyclo[3.1.0]hexanes (bicyclization products).

Aryl lithium reagents, complexed with (-)-sparteine, react enantioselectively with cyclic meso epoxides, to afford chiral aryl cyclanols. The enantiomeric excess, though moderate (27-87%), is the best in the literature for such a reaction. Activation by BF3 · OEt2 is needed, and is compatible with a diamine such as (-)-sparteine.

Lithiation of N -Boc-4,4-dimethyl-1,3-oxazolidine with s -BuLi and the following reaction with benzaldehyde was carried out in the presence of (−)-sparteine. The reaction was not diastereoselective ( syn : anti =46:54), but each isomer of the adducts was obtained enantioselectively ( syn : 90% ee, anti : 88% ee). Addition of MgBr 2 to the reaction mixture increased the diastereoselectivity to syn : anti =90:10.